POS1203 INCREASED PROTEASE-ACTIVATED RECEPTOR 1 AUTOANTIBODIES ARE ASSOCIATED WITH SEVERE COVID-19
Authors: F. Tran, A. Scharmacher, H. Grasshoff, S. Schinke, N. Kaeding, J. Bernades, J. Y. Humrich, O. Cabral-Marques, K. Gaede, C. Lange, J. Rupp, P. Rosenstiel, B. F. Hoyer, K. Schulze-Forster, H. Heidecke, G. Halpert, H. Amital, Y. Shoenfeld, S. Schreiber, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2022)

Background In acute COVID-19 infection, growing evidence hints towards a broad activation of plasma cells and the presence of pathologic autoantibodies (abs). A systematic screening for abs confirmed induction of diverse functional abs by SARS-CoV-2 infection (1, 2). Immune-mediated thrombosis, involving platelet activation, has been identified as one of the key pathogenic mechanisms in COVID-19 and is linked to morbidity and mortality (3). As natural abs against G protein-coupled receptors, functional abs against the thrombin receptor type-1 (PAR-1) might predispose for increased activation of the coagulation system present in COVID-19 infection. Objectives The aim of this study is to identify the diagnostic value of anti-PAR1 antibodies and their capacity to predict the outcome of COVID-19 infection. Methods 82 serum samples from 55 individuals with COVID-19 derived from three different hospitals in Schleswig-Holstein, Germany, and 88 single time point samples from healthy controls were subjected to ELISA-based quantification of anti-PAR-1 abs (CellTrend GmbH Luckenwalde, Germany). The levels of anti-AT1R abs were compared with clinical and laboratory parameters. Results COVID-19 patients revealed markedly increased levels of circulating anti-PAR1 abs in hospitalized patients particularly in those required intensive care treatment in comparison to controls (p &lt; 0.0001, Figure 1a). Anti-PAR1 ab levels were highest in patients with fatal outcome (p = 0.006, Figure 1a). Receiver operating characteristic (ROC) analysis of PAR1 abs levels in COVID-19 patients revealed a sensitivity of 84.00% and a specificity 79.25% for patients requiring intensive care unit (ICU) treatment and a sensitivity of 87.50 % and a specificity 84.51 % to distinguish fatal vs. non-fatal disease outcome (Figure 1b). We found correlation of circulating anti-PAR1 abs with D dimers. Figure 1. Levels of anti-PAR-1 abs in healthy controls (HC) versus COVID-19 positive patients with different disease severity and in non survivors (left). ROC curves are shown to discriminate patients requiring intensive care unit (ICU) or survivors in COVID-19 infection. Conclusion The increased anti-PAR1 abs, their prediction to identify patients requiring ICU and fatal outcome, and the correlation with markers for blood clotting suggest a role for antibodies against PAR1 in the disease development of blood clotting in COVID-19. References [1]Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science 2020: 370(6515). [2]Wang EY, Mao T, Klein J, et al. Diverse functional autoantibodies in patients with COVID-19. Nature 2021. [3]Bonaventura A, Vecchie A, Dagna L, et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol 2021: 21(5): 319-329. Disclosure of Interests None declared